It is well established that the Rb and E2F protein family members are important regulators of (GI to S phase progression and apoptosis. Moreover, mutations in the "Rb/E2F pathway" are important contributors to human neoplasia. Therefore, it is important to understand how Rb and E2F proteins regulate both cell cycle and death. However, studies of mammalian Rb and E2F function have been hindered by the lack of a suitable genetic system and by the large family of Rb and E2F genes. Studies of Rb and E2F function in Drosophila are ideal since these gene families are smaller and the development and genetic manipulation of the organism is well understood. Therefore, the proposed research aims to identify important regulators of Rbf and dE2F activity in vivo. In the first approach, both novel preexisting and prospective dE2F- and Rbf-dependent phenotypes will characterized in vivo. In the second approach, mutations in genes which modify these phenotypes will be isolated using a genetic screening strategy. This approach has the ability to identify new proteins involved in Rbf and dE2F function that have not been identified in mammalian systems. Identification of novel regulators of both Rbf and dE2F function will facilitate our understanding of the function of these genes in vivo and ultimately during development and tumorigenesis.